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Pathway analysis of differentially expressed genes in patients with acute aortic dissection
Salah A Mohamed1, Hans H Sievers, Thorsten Hanke
1Department of Cardiac Surgery, University Clinic of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
Background:
Acute aortic dissection (AAD) is a life-threatening condition with high mortality and a relatively unclarified pathophysiological mechanism. Although differentially expressed genes in AAD have been recognized, interactions between these genes remain poorly defined. This study was conducted to gain a better understanding of the molecular mechanisms underlying AAD and to support the future development of a clinical test for monitoring patients at high risk.
Materials And Methods:
Aortic tissue was collected from 19 patients with AAD (mean age 61.7 +/- 13.1 years), and from eight other patients (mean age 32.9 +/- 12.2 years) who carried the mutated gene for Marfan syndrome (MS). Six patients (mean age 56.7 +/- 12.3 years) served as the control group. The PIQOR(TM) Immunology microarray with 1076 probes in quadruplicates was utilized; the differentially expressed genes were analysed in a MedScan search using Pathway Assist software. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and protein analysis were performed.
Results:
Interactions of MS fibrillin-1 (FBN1) in the MedScan pathway analysis showed four genes, fibulin-1 (FBLN1), fibulin-2 (FBLN2), decorin (DCN) and microfibrillar associated protein 5 (MFAP5), which were differentially expressed in all tissue from AAD. The validation of these genes by qRT-PCR revealed a minimum of three-fold downregulation of FBLN1 (0.5 +/- 0.4 vs. 6.1 +/- 2.3 fold, p = 0.003) and of DCN (2.5 +/- 1.0 vs. 8.5 +/- 4.7 fold, p = 0.04) in AAD compared to MS and control samples.
Conclusions:
Downregulation of fibrillin-1 (FBN1) may weaken extracellular components in the aorta and/or interfer with the transmission of cellular signals and eventually cause AAD. Additional research on these four identified genes can be a starting point to develop a diagnostic tool.
Insights
This study identifies four key genes (FBLN1, FBLN2, DCN, MFAP5) involved in acute aortic dissection (AAD). Downregulation of FBLN1 and DCN suggests a potential mechanism for AAD development and diagnostic markers.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Genetics
Background:
- Acute aortic dissection (AAD) is a critical condition with high mortality and unclear molecular mechanisms.
- Understanding gene interactions in AAD is crucial for developing diagnostic and therapeutic strategies.
Purpose of the Study:
- To investigate the molecular mechanisms underlying AAD by analyzing differentially expressed genes.
- To identify potential biomarkers for monitoring high-risk patients.
Main Methods:
- Gene expression profiling using the PIQOR(TM) Immunology microarray on aortic tissue from AAD patients, Marfan syndrome (MS) patients, and controls.
- Pathway analysis using MedScan and Pathway Assist software.
- Validation of differentially expressed genes using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and protein analysis.
Main Results:
- Pathway analysis identified four differentially expressed genes (FBLN1, FBLN2, DCN, MFAP5) associated with fibrillin-1 (FBN1) in AAD.
- qRT-PCR confirmed significant downregulation of fibulin-1 (FBLN1) and decorin (DCN) in AAD patients compared to MS and control groups.
- FBLN1 showed a minimum three-fold downregulation (p = 0.003) and DCN showed downregulation (p = 0.04) in AAD.
Conclusions:
- Downregulation of FBN1 may compromise aortic extracellular components and disrupt cellular signaling, potentially leading to AAD.
- The identified genes (FBLN1, FBLN2, DCN, MFAP5) represent a promising starting point for developing diagnostic tools for AAD.
- Further research into these genes could enhance early detection and risk stratification for AAD.
